Modulation of Cytotoxicity of Benzamide Riboside by Expression of NMN Adenylyltransferase
NAD has important regulatory role in repair of DNA damage and cell growth since it is a substrate for poly(ADPribose) polymerase (PARP). PARP appears to direct short-patch base excision repair and induce p53 upregulation leading to apoptosis. BR inhibits PARP at high concentrations when assayed in permeabilized leukemic cells. Several other IMPDH inhibitors (TR, mycophenolic acid, and ribavirin) exhibit similar PARP inhibitory activity. Although this inhibition was reversible, it was not prevented by the addition of guanosine, GTP, or its nonhydrolyzable analog γ-S-GTP. Therefore, it can be concluded that IMPDH inhibitors directly inhibit PARP. Presumably, the shared IMP-NAD active site of IMPDH has a similar architecture to the NAD-binding pocket of PARP.
Keywords: antimetabolites; apoptosis; growth inhibition; imp dehydrogenase(impdh); inosine 5-monophosphate dehydrogenase(impdh); nmn adenylyltransferase; poly(adp-ribose)polymerase(parp); selenazofurin; tiazofurin
Document Type: Review Article
Publication date: 2002-04-01
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